Method and apparatus for performing hematologic analysis using an array-imaging system for imaging and analysis of a centrifuged analysis tube

ABSTRACT

A method and device for analyzing a hematologic sample centrifuged within a capillary tube is provided. The device includes a tube holder, a sample imaging device, a processor, and a sample data display. The sample imaging device is operable to create a digital image of the sample within a region of the tube. The region is defined by substantially all of the radial width and axial length of the sample residing within the internal cavity of the tube in the region where the float resides after centrifugation. The sample imaging device is operable to produce signals representative of the image. The processor is adapted to produce information relating to bands of interest within the image based on the signals from the sample imaging device. The sample data display is adapted to display the results therefrom and/or a digital image of the sample within the region.

This application claims the benefit of U.S. Provisional PatentApplication No. 61/305,449 filed Feb. 17, 2010 and U.S. ProvisionalPatent Application No. 61/351,138 filed Jun. 3, 2010, each of whichapplications is hereby incorporated by reference in its entirety.

BACKGROUND INFORMATION

U.S. Pat. Nos. 4,027,660; 4,091,659; 4,137,755; 4,209,226; 4,558,947;4,683,579; 5,132,087; 5,888,184; and 6,441,890 describe methods andapparatus for hematological analysis using a capillary tube and a spaceoccupying insert that floats on the centrifuged red blood cells therebyexpanding the surrounding buffy coat and permitting the measurement andquantization of the blood's layers. This method permits thedetermination of a compete blood count (CBC) consisting of hematocrit, ahemoglobin determination, a total white blood cell count with the latterpresented as a total and percent granulocytes and total and percentlymphocytes plus monocytes, as well as a platelet count and a mean redcell hemoglobin concentration. It is widely used through the world forperforming point of care CBC in human and veterinary medicine. Thedevice, formerly manufactured and sold by Becton Dickinson, Inc. of NewJersey U.S.A. is now manufactured and sold by QBC Diagnostics, Inc., ofPennsylvania, U.S.A. The apparatus is sold under the trademark of QBC®hematology. The capillary tubes are referred to in the industry as “QBC®tubes”.

The QBC® hematology system includes a number of different complexinstruments for reading the QBC® tubes, each of which has anillumination system, a power source, an imaging and optical system, amicroprocessor, and a display. These devices can cost anywhere fromseveral hundred to many thousands of U.S. dollars. The current versionsof both the stand-alone reader and the integral reader-centrifuge (QBC®STAR reader) provide for a linear scan of the tube, either while it isstationary in the case of the stand-alone reader or while the centrifugeis in motion, as is the case with the QBC® STAR reader. In both cases,the linear scan is limited to scanning a single axially extending linescan of the tube, which evaluates only a thin stripe of the area ofinterest within the tube. Because this method of scanning can only scana thin stripe of the area of interest at a given time, it is necessaryto take multiple axially extending scans taken at differentcircumferential positions of the tube to determine which of the scanscan be used for analytical purposes. By looking at several differentscans, each taken at a different circumferential position, it ispossible to ascertain whether any particular scan is representative ofthe sample or if it contains an unrepresentative anomaly. Also, becauseof the narrow scan, the mechanical and optical alignment of theinstrument must be held to a very high tolerance, which also increasesthe cost of the device.

This is particularly true in the case of the QBC® STAR reader, becausethe QBC® tube is read while the centrifuge is in motion, necessitatingan elaborate timing system to ensure that illumination occurs exactlywhen the tube is in position under the linear scanning device (e.g., CCDscanner). Another, related problem is the need to provide elaboratevibration damping so that the relative tube and reader position bemaintained during this process.

These considerations force the analysis tube readers to have arelatively high price, which limits the market size for the QBC®hematology system because health care providers are reluctant and/orunable to make the requisite equipment investment when the equipment isonly used for a few tests per day. In those instances when the point ofcare giver does not have the analysis equipment, the patient issubjected to the significant inconvenience, harm and expense of havingto go to a private laboratory and having to wait often several days toget the result. The lack of an analysis device also makes thephysician's job more difficult by precluding immediate results at thepoint of care. Additionally, regulatory requirements of the UnitedStates require that the providers of the test be subject to regulatorysupervision under the CLIA (Clinical Laboratory Improvement Act) laws.

What is needed, therefore, is a simple, inexpensive, robust method forreading the centrifuged blood sample at the point of care with immediateavailability of results while the health care providers are still withthe patient. In addition, a method and device are needed that canprovide accuracy results and methodological adherence to proper analytictechniques, as well as quality control measures, particularly those thatwill permit CLIA waiving, which is subject to less burdensomeregulations.

SUMMARY OF THE INVENTION

According to one aspect of the present invention, a device for analyzinga hematologic sample centrifuged within a capillary tube is provided.The tube has an internal compartment with a radial width and an axiallength and a float disposed within the tube. The device includes a tubeholder, a sample imaging device, a processor, and a sample data display.The sample imaging device is operable to create a digital image of thesample within a region of the tube. The region is defined bysubstantially all of the radial width and axial length of the sampleresiding within the internal cavity of the tube in the region where thefloat resides after centrifugation. The sample imaging device isoperable to produce signals representative of the image. The processoris adapted to produce information relating to bands of interest withinthe image based on the signals from the sample imaging device. Thesample data display is adapted to display the results therefrom and/or adigital image of the sample within the region.

According to another aspect of the present invention, a method ofanalyzing a hematologic sample deposited within a capillary tube isprovided. The tube has an internal cavity with a radial width and anaxial length, and a float disposed within the tube. The method includesthe steps of: a) centrifuging the sample to create constituent bandswithin the sample disposed in the tube; b) creating an image of a regionof the centrifuged sample, which region is defined by substantially allof the radial width and axial length of the sample residing within theinternal cavity of the tube in a region where the float resides aftercentrifugation; c) determining a position for one or more bandboundaries using the image; and d) producing analysis results based onthe determined band boundaries.

Advantages associated with the present analysis device include theprovision of a less expensive, and easier to manufacture, analysisdevice. The imaging of substantially all of the radial width and asignificant portion of the axial length of a centrifuged sample within acapillary tube eliminates many problems associated with narrow lineararray sensing. For example, prior art linear array sensing issusceptible to circumferentially located bandwidth anomalies; e.g., ifthe bandwidth at a particular circumferential position is irregularlytoo small or too big, data based on that band width will be inaccurate.For this reason, the prior art devices take multiple linear arraysensings at non-contiguous circumferential positions and average thosesensings, or otherwise compare them to one another for accuracy. Theprior art devices, therefore, require hardware that can rotate one orboth of the linear sensing array and the sample. The hardware must alsobe able to provide very accurate mechanical and optical alignment of theinstrument relative to the sample, and in the case of a dynamic sensingdevice like the QBC® STAR reader, also provide elaborate imagingcontrols and vibration damping. The present device also providessignificant quality control mechanisms.

On the other hand, the prior art linear imaging had the advantage ofminimal geometric distortion. Since all prior art imaging data was inthe form of a narrow linear segment taken at a right angle to the tubeas it was scanned, each band position was exactly related to its digitalrepresentation. In the case of the image array as used in the presentdevice, in which the tube is positioned some distance from the imaginglens and camera, the bands in the tube are foreshortened in proportionto their distance from the center of the optical axis, and the sides ofthe tube are particularly affected by this effect, sometimes making themappear crescent shaped. This geometric distortion, in addition to anyother distortions from the lens, is preferably accounted for in order toenhance the accuracy of the results. For example, the geometricdistortion can be accounted for by using a correction table whichaccounts for each pixel, or regions in the image. The correction tablecan be used to re-map the image so that the image positions correctlycorrespond to the actual locations on the tube surface. This type ofcorrection table can be automatically generated by imaging and analyzinga known ‘calibration’ standard or if only geometric distortion isinvolved, the corrections can be simply calculated based on the knowndistances involved. Alternatively, the geometric distortion can beaccounted for by correcting the band lengths following their preliminarymeasurement.

The foregoing and other objects, features and advantages of the presentinvention will become more apparent in light of the following drawingsand detailed description of the present invention.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic diagram of the present invention hematologyanalysis device.

FIG. 2 is a schematic diagram of a capillary tube.

FIG. 3 is an enlarged partial view of a tube such as that shown in FIG.2.

DETAILED DESCRIPTION OF THE INVENTION

Referring to FIGS. 1-3, a blood sample for analysis within the QBC®hematology system is typically obtained either from a venous orcapillary sample, centrifuged in a simple, small dedicated centrifugewhich may be either battery powered or AC powered. U.S. Pat. Nos.4,027,660; 4,683,579 and 6,441,890, each of which is hereby incorporatedby reference in its entirety, describe methods and apparatus forhematological analysis using a capillary tube and a space occupyinginsert that floats on the centrifuged red blood cells thereby expandingthe surrounding buffy coat and permitting the measurement andquantization of the blood's layers. The capillary tube 10 includes abody that extends between a closed bottom 12 and an open top 14. In someembodiments, the “closed bottom” may be vented to allow the escape ofgas. The open top 14 provides access to an internal cavity 16 that has aradial width 18 and an axially extending length 20. In those embodimentswhere the tube 10 is cylindrical, the radial width 18 is the innerdiameter of the tube 10. The present invention is not limited to usewith any particular type of capillary tube. U.S. Pat. No. 4,027,660, forexample, describes a QBC® style capillary tube operable to contain afluid sample and a volume occupying mass 22 (hereinafter referred to asa “float”), and the information available by virtue of the relativepositioning of the float 22 within the sample after centrifugation. U.S.Pat. No. 6,444,436 describes a different style of capillary tube thatcan be used with the present invention; e.g., one having a polynomial(e.g., rectilinear) cross-sectional geometry. FIGS. 2 and 3 of thepresent application diagrammatically illustrate a capillary tube 10 witha sample and a float 22 disposed in the internal cavity 16 of the tube10. The centrifuged sample disposed in the tube 10 illustrates theconstituent bands 24 (24 a, 24 b, 24 c, 24 d, 24 e) and the bandboundaries 25 (25 a, 25 b, 25 c, 25 d) therebetween. U.S. Pat. Nos.4,683,579 and 6,441,890 describe automated devices for reading thecentrifuged sample by way of an axially extending linear scan of alimited portion of the sample disposed within the QBC® tube, whichlimited linear portion is disposed at a particular circumferentialposition of the tube 10.

The present invention analysis device operates with a capillary tube 10such as those provided within a QBC® hematology system; i.e., a tube 10filled with a sample that has been centrifuged to produce the separatedconstituent layers (i.e., “bands”) 24 within the sample. One embodimentof the present analysis device 28 includes a housing 30 containing atube holder 32, a sample imaging device 34, a processor 36 adapted toproduce information relating to bands 24 of interest within the imagebased on the signals from the sample imaging device 34, a sample datadisplay 38, and may include an operator input device 40 that enables theoperator to enter relevant patient information.

In some embodiments, the analysis device 28 further includes acentrifuge 42 with a platen 44 configured to hold one or more capillarytubes 10 in a position where the tubes 10 extend radially outward from acentral axis. In these embodiments, the analysis device 28 can performboth the centrifugation and the image analysis. The centrifuge 42 isoperable to centrifugally spin the tube 10 containing the sample aboutthe central axis at speeds sufficient to create constituent layerseparation within the sample disposed in the tube 10. In theseembodiments, the platen 44 is an example of a tube holder 32. In otherembodiments, the tube holder 32 may be independent of the centrifuge 42.

The sample imaging device 34 includes a digital camera operable to imagesubstantially all of the radial width 18 and axial length 20 of thesample residing within the internal cavity 16 of the tube 10 in theregion 46 (see FIG. 3) where the float 22 resides after centrifugationin a single image, and to produce signals representative of the image.In the preferred embodiments, the sample imaging device 34 is operableto image a region 48 comprising substantially all of the radial width 18and axial length 20 of the sample within the tube 10 in a single image,and to produce signals representative of the image. Alternately, two ormore cameras can be used to image separate portions of the tube 10,which portions are contiguous with one another. The images of thecontiguous regions can be subsequently combined and analyzed or areseparately analyzed. Either the digital camera itself, or an independentlight source within the sample imaging device 34, provides sufficientlighting so that bands 24 of interest within the centrifuged sample maybe differentiated within the sample image. The optical resolution of thecamera must be sufficient to provide adequate clarity within the imagefor the analysis at hand; e.g., to differentiate bands 24 of interest.As indicated above, the sample imaging device 34 may be incorporatedinto a QBC® tube type reader, or may be an independent device (e.g., aportable digital camera, a cell phone camera, etc.) configured for usewith such a reader. An example of an acceptable digital camera is aBayer-type matrix color camera. If, for example, a standard Aptina® fivemegapixel color camera chip with a frame width of 2592 pixels is used,it can produce a theoretical image resolution of 0.02 mm, which isacceptable for most analyses. If a color camera is used, color filtersand different illumination types are likely not required. A grey scaledcamera may also be used because the separated buffy coat layers havedifferent light scattering properties and may therefore be detectedusing a black and white camera, although this measurement is less robustand requires more controlled illumination. The sample imaging device 34may be described as an “area-array imaging device” because it imagessubstantially all of the radial width 18 and axial length 20 of thesample within the interior cavity 16. If a plurality of cameras is usedwithin the present sample imaging device 34, the images they produce arecontiguous with one another thereby permitting the plurality of imagesto be combined into a single representative image. The linear scandevices of the prior art, in contrast, are limited to producing narrowlinear segments that do not extend across the full radial width 18, andthe circumferential linear segments are not contiguous with each other.As a result, the circumferentially positioned linear segments cannot becombined into a single representative image. Examples of acceptableindependent light sources include white and/or blue LEDs, operableeither in a steady state mode or in the case of the QBC® STAR typereader, in a pulsed mode. The relative blue spectrum of a white LED orthe inclusion of a separate blue LED can excite the fluorescence of adye such as Acridine Orange in the tube 10.

The processor 36 is adapted (e.g., programmed) to perform several tasks,including: a) controlling the sample imaging device 34 based on theanalysis at hand; b) controlling the centrifuge 42 for those embodimentsthat include one; c) receiving and acting on operator input enteredthrough the operator input device 40; and d) producing informationrelating to bands 24 of interest within the image based on the signalsfrom the sample imaging device 34. The extent of the informationrelating to the bands 24 can vary depending upon the embodiment of thedevice 28. For example, the processor 36 may be adapted to provideinformation relating to the adequacy of the sample image, and/or withalgorithmic capability that is operable to analyze the signalsrepresentative of the sample image and produce data (e.g., CBC,hematocrit, WBC count, etc.) relating thereto based on characteristicsof the different bands 24 within the centrifuged sample. In someapplications, the processor 36 can be adapted to produce graphicmarkings based on the analysis of the sample that can be superimposedover the sample image when displayed to illustrate the calculated bandboundaries 25 relative to the sample image. Using the analysis of ablood sample as an example, graphic markings can be used to identifyfeatures such as the: a) bottom of the tube 10; b) bottom of the float22; c) red blood cell/granulocyte interphase; d) granulocyte/lymphocyteand monocyte interphase; e) lymphocyte and monocyte/platelet interphase;f) platelet/plasma interphase; g) top of the float 22; h) plasma/airinterphase; etc.

The sample data display 38 is in communication with the processor 36 andincludes a display screen. The display screen is an electronic screen(e.g., flat screen LED, LCD, etc.) operable to display the calculatedresults and/or a digital image of the sample residing within thecentrifuged sample with sufficient optical resolution so that the imagecan be evaluated by a technician operator to provide the informationpertaining to the bands 24 of interest within the centrifuged sample. Inthose embodiments that include an operator input device 40 (e.g., keypad, touch screen, etc.), the operator input device 40 allows theoperator to enter relevant patient or other information, if desired. Thesample display 38 may be integral with the housing 30, or it may be anindependent device in communication with the processor 36. For example,universal monitors are often used in medical facilities, which monitorshave the capability of displaying data from more than one analysisdevice. In such an application, the data to be displayed may be viewedon an integral display screen and/or a remotely located display devicein communication with the processor 36.

In some embodiments, the analysis device 28 includes a communicationport 50 for sending the signals representative of the sample image to aremote location. The communication port 50 can be a hardwire port forcommunicating by hardwire connection to a remote site, or it can be awireless communication connection (e.g., similar to that used in awireless phone).

In some embodiments, fiduciary marks 52 (i.e., calibration, measurementmarks, etc.) may be placed on or in the capillary tube 10, or the tubeholder 32, or on a measuring device positioned adjacent the tube 10(e.g., a ruler) to facilitate geometric and/or optical calibration andthereby account for any image distortion introduced by the camera. Inthose instances where the fiduciary marks are placed on or in the tube,a particularly useful embodiment is one wherein the marks are positionedrelative to the internal cavity to permit geometric evaluation of samplewithin the internal cavity. In those instances where fiduciary marks 52are disposed on a measuring device positioned adjacent the tube 10, themeasurement device can measure along an axis that is maintained parallelto the lengthwise axis (e.g., axial direction) of the tube 10. In suchembodiments, the measurement device is preferably in close proximity(e.g., in the same focal plane) as the sample tube 10. Alternately, alook-up-table can be provided by factory calibration to serve thisfunction. During the image processing and analysis steps, thecalibration information can be used to ensure correct lengthmeasurements of the tube 10 features, regardless of their position inthe image frame or distance from the camera and can compensate forinstrument-to-instrument differences.

Operation:

A fluid sample (e.g., whole blood) is collected from a patient anddeposited into a capillary tube 10 such as those used in the QBC®hematology system for subsequent centrifugation. As indicated above, thecentrifuge may be independent of, or incorporated into, the analysisdevice 28. The sample is centrifuged for a period of time adequate tocreate constituent layer separation within the sample disposed in thetube 10, and the representative bands 24 associated therewith. Thecentrifuged sample is then imaged using the sample imaging device 34.The image includes substantially all of the radial width 18 and axiallength 20 of the sample residing within the internal cavity 16 of thetube 10 in the region where the float 22 resides after centrifugation.Because capillary tubes 10 are not always filled with the exact samevolume of fluid sample, the sample imaging device 34 preferably imagesthe region 48 of the tube 10 from the top meniscus to the bottom of thered blood cell layer. It is desirable, but not required, that the bottomof the tube 10 be imaged as well. If the sample being imaged is disposedwithin a STAR type QBC® tube, for example, the total length between thetube bottom to the tube top fill position is approximately 53 mm. Thedistance from the tube top fill position to the bottom of the float 22in most instances is about 37 mm. In those device 28 embodiments thatinclude a centrifuge, the sample may be centrifuged and the centrifugesubsequently stopped or slowed to a very low RPM prior to the imaging.The sample imaging device 34 produces signals representative of eachimage and communicates those signals to the processor 36.

The images signals are subsequently analyzed within the processor 36using image processing algorithms to isolate and analyze the bands 24 ofinterest within the sample, and in some instances relevant sections ofthe bands 24. Before or after the image signals are analyzed, the imagesignals may be sent to the sample data display 38 for evaluation by theoperator. The ability to have an operator visually evaluate an imagethat includes substantially all of the radial width 18 of the samplewithin the tube 10, and a relevant portion of the axial length 20 of thesample is a substantial advancement of the technology. A person of skillin the art will recognize that no automated system can account for allpotential variables within the sample image. For example, during thecentrifugation process, there is a chance that sample will exit thecapillary tube 10 and pass into the retaining tube of the centrifuge. Insuch instances, the released sample can contaminate the exterior of thecapillary tube 10 and inhibit accurate analysis. Similarly, a misplacedtube label or debris deposited on the exterior of the capillary tube 10during handling can also inhibit or prevent accurate analysis. In theseinstances, the ability of the present device 28 to produce a singlesubstantially complete image of the centrifuged sample will enable theoperator to identify such potential problems and take appropriateaction. As another example, the image available with the present device28 will also enable the operator to evaluate other aspects of the sampleimage for potential problems; e.g., overall image quality, accuracy ofsample coloration, the degree to which a blood sample may be lipemic oricteric, etc. In those applications where the operator evaluates theimage after processing and boundary markings are assigned by theprocessor 36, the operator can evaluate whether the assigned boundarymarkings are accurately positioned relative to the sample image. Hence,the ability to have an operator visually evaluate an image using thepresent device 28 provides considerable quality controls to the analysisprocess. It should be emphasized that the present instrument, asdescribed herein, may be used in locations where trained operators arepresent, and also locations where no trained operators are present(e.g., a CLIA-waived environment). In the latter type location, thesample images captured by the present device 28 may be sent to aremotely located trained operator for analysis. If it is not possible tohave a trained operator review the image and/or results within apredetermined period of time, the present device 28 may be programmed toprevent the release of any data if the sample image has any detectableanomalies. A visual image analysis is preferable in that the criteriafor analysis rejection can be loosened, but a purely automated analysis(e.g., that checks for anomalies) is preferable to no analysis at all.

The extent to which the present device 28 images the centrifuged samplewithin the tube 10 makes possible another quality control mechanism. Asindicated above, the present device 28 images substantially all of theradial width 18 and a significant portion of the axial length of thecentrifuged sample. In some instances, the radial portion of the imagecan be expanded to a point outside of the capillary tube 10 to includeother imageable features such as calibration markers or areas. The imagecharacteristics associated with the regions outside of the capillarytube 10 can be compared against the characteristics of the region insidethe tube 10. Inconsistencies identified by the comparison of thecharacteristics (e.g., brightness) can be used to evaluate the accuracyof the image. This type of quality control is not possible using theprior art reading devices that utilize a linear scanning device, whichhas essentially only a one pixel width.

Although the invention has been described and illustrated with respectto exemplary embodiments thereof, the foregoing and various otheradditions and omissions may be made therein and thereto withoutdeparting from the spirit and scope of the present invention.

1. A device for analyzing a hematologic sample centrifuged within acapillary tube, which tube has an internal compartment with a radialwidth and an axial length and a float disposed within the tube, thedevice comprising: a tube holder; a sample imaging device, operable tocreate a digital image of the sample within a region of the tube, whichregion is defined by substantially all of the radial width and axiallength of the sample residing within the internal cavity of the tube inthe region where the float resides after centrifugation, and to aproduce signals representative of the image; a processor adapted toproduce information relating to the image based on the signals from thesample imaging device; a sample data display adapted to display theinformation relating to the digital image of the sample within theregion.
 2. The device of claim 1, wherein the sample data display isfurther adapted to display the information from the processor.
 3. Thedevice of claim 1, further comprising a communication port adapted tosend the signals representative of the image to a location remote fromthe device.
 4. The device of claim 1, further comprising a centrifugewith a platen configured to hold at least one capillary tube in aposition where the tube extends radially outward from a central axis,and is operable to centrifugally spin the tube containing the sampleabout the central axis at speeds sufficient to create constituent layerseparation within the sample disposed in the tube.
 5. The device ofclaim 1, wherein the sample imaging device includes one or more digitalcameras.
 6. The device of claim 5, wherein the digital camera isoperable to create a single image of the region of the tube, wherein theregion is defined by substantially all of the width and axial length ofthe sample within the tube.
 7. The device of claim 5, wherein thedigital camera is a Bayer-type matrix color camera.
 8. The device ofclaim 5, wherein the digital camera is a grey-scaled black and whitecamera.
 9. The device of claim 1, wherein the tube holder, sampleimaging device, processor, and sample data display are mounted in or ona housing.
 10. A method of analyzing a hematologic sample depositedwithin a capillary tube, which tube has an internal cavity with a radialwidth and an axial length, and a float disposed within the tube, themethod comprising the steps of: centrifuging the sample to createconstituent bands within the sample disposed in the tube; creating animage of a region of the centrifuged sample, which region is defined bysubstantially all of the radial width and axial length of the sampleresiding within the internal cavity of the tube in a region where thefloat resides after centrifugation; determining a position for one ormore band boundaries using the image; and producing analysis resultsbased on the determined band boundaries.
 11. The method of claim 10,further comprising the step of displaying the image.
 12. The method ofclaim 11, further comprising the step of superimposing graphic markingsin the displayed image at positions of the determined band boundaries.13. The method of claim 10, wherein the image is created using a digitalcamera.
 14. The method of claim 13, wherein the step of creating theimage includes creating a single image of the region of the tube usingthe digital camera, wherein the region is defined by substantially allof the width and axial length of the sample within the tube.
 15. Themethod of claim 10, further comprising the step of transmitting theimage of the region of the centrifuged sample tube to a location remotefrom an image location where the image was created.
 16. The method ofclaim 15, further comprising the step of analyzing the image at theremote location and producing data relating to the analysis, andtransmitting the analysis data back to the image location.
 17. Themethod of claim 15, further comprising the step of analyzing the imageat the remote location for quality control and producing quality controldata, and transmitting the quality control data back to the imagelocation.
 18. A capillary tube, comprising: a body having an internalcavity, an open top, and a vented bottom, wherein the internal cavityextends between the open top and the vented bottom, and is sized topermit the entry of liquid into the internal cavity through the open topby capillary action; and fiduciary marks on or in the body, which marksare operable to permit geometric evaluation of sample within theinternal cavity.
 19. The tube of claim 18, wherein the fiduciary marksare positioned relative to the internal cavity to permit geometricevaluation of sample within the internal cavity.
 20. The tube of claim18, wherein the body is a generally cylindrical.